The most common methods currently in use for the treatment of cancer include surgery, radiation therapy, and chemotherapy. While these therapies are successful for some forms of the disease, they are far from universally successful in curing cancer. Moreover, traditional therapeutic regimens often cause adverse side effects such as nausea, vomiting, cardiac toxicity, bone marrow suppression, and secondary cancer. Vitamin C (ascorbic acid, ascorbate) has been proposed as an alternative to chemotherapy or as an adjuvant to lessen side effects associated with it. (For the purposes of this application, a reference to ascorbic acid includes the anionic component, ascorbate whether as an acid or one of the pharmaceutically acceptable salt thereof, most notably including sodium ascorbate and calcium ascorbate, any of which are included in a reference to "ascorbic acid" or "ascorbate"). Ascorbic acid has been thought by some to improve immune response and to prevent tumor spreading by strengthening extracellular matrix, but these theories have not as yet been conclusively proven. Clinical trials with ascorbate at doses on the order of 10 g/day were successful in some cases, but not in others. At very high doses, ascorbic acid is preferentially toxic to tumor cells. This preferential toxicity is understood to relate to the ascorbate mediated production of hydrogen peroxide, which is more toxic to tumor cells due to the lower levels of catalase typically present in tumor cells as compared to normal cells. High dose intravenous ascorbate has thus been suggested for the treatment of cancer, as described in U.S. Pat. No. 5,639,787.
Critical to the use of high dose intravenous ascorbate as an anti-cancer agent is the ability to clinically achieve plasma ascorbate levels sufficient to kill tumor cells. Previous measurements of ascorbate plasma levels following intravenous infusion demonstrate concentrations greater than those needed to kill tumor cells grown in monolayer cultures in vitro. However, much higher levels of ascorbate are required to kill tumor cells grown as three-dimensional in vitro tumors. Using the hollow fiber "solid" tumor model, it has been observed that ascorbate concentrations in excess of 500 mg/dL may be required to effectively treat tumors. Currently, the maximum plasma ascorbic acid concentration generally achievable in humans by intravenous infusion is roughly 500 mg/dL, a peak level that drops off sharply over a relatively short period of time. Although ascorbate is relatively innocuous to human patients, the need for higher plasma concentrations demonstrates a need either to safely raise effective plasma levels of ascorbate or to increase the cytotoxic effectiveness of ascorbate toward cancer cells to decrease the required dosage.